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Biomedical subjects

D I Smith

Publications and source records attributed to D I Smith.

At least 127 records · Page 7Linked to original sources

Anesthesia effects: auditory brain-stem response.

Auditory brain-stem responses (ABRs) were measured in the awake state and with ketamine and xylazine anesthesia in adult gerbils. Surface recorded vertex-positive components of the ABR were analyzed with respect to the awake and anesthetized states as a function of stimulus frequency. ABR thresholds were not altered with ketamine/xylazine. Small increases in peak latency were associated with anesthesia for all components except wave P1. Increases in absolute latency were progressively greater for successive peaks, reaching an average shift of 0.41 msec for wave P6. Amplitude changes with anesthesia were more variable, with increases generally seen for waves P4 and P6. Significant anesthesia effects on peak latency and amplitude were independent of stimulus frequency. These data confirm previously reported ABR sensitivity to non-barbiturate anesthesia. Direct comparisons of ABR interpeak intervals or amplitude ratios from awake versus anesthetized animals must account for the effects of barbiturate and non-barbiturate agents. However, the stability of response threshold and the small magnitude of latency and amplitude changes with a ketamine and xylazine regimen demonstrate that accurate electrophysiological measures of hearing sensitivity and auditory brain-stem activity can be obtained in anesthetized animals, provided that temperature and other parameters are maintained within normal physiological limits.

Anesthesia↗

Relationship between alcohol consumption and breast cancer morbidity rates in Western Australia, 1971--1984.

Per adult (greater than or equal to 15 years) consumption of beer, wine, spirits and absolute alcohol for a 14-year period (1971--1984) was related to female breast cancer morbidity rates in Western Australia. Mann-Whitney U-tests showed that during the 7 years of highest wine consumption the highest rates for breast cancer occurred for females aged 30--59 years, but for women over 60 years of age the result was insignificant. The findings are consistent with a number of previous studies which have shown a positive association between alcohol consumption and increased risk of breast cancer.

Adult↗

Middle latency response: frequency and intensity effects.

Auditory middle latency responses (MLR) and auditory brainstem responses (ABR) were measured with epidural electrodes in unanesthetized gerbils. Response thresholds of simultaneously recorded MLRs and ABRs, and latencies and amplitudes of MLR peaks were analyzed with respect to stimulus intensity (10-80 dB SPL) and frequency (0.5, 1, 2, 4, 8 and 16 kHz). Only minor changes in the latencies of the MLR were associated with increases in stimulus intensity. Changes in latencies were more apparent for waves A and B as compared to wave C, and were significant only at low intensities. Latencies did not change significantly as a function of stimulus frequency. Amplitudes of the MLR were highly variable between animals, particularly waves B and C, and showed complex changes with intensity. In general, wave amplitudes were inversely related to stimulus frequency. The gerbil MLR resembles MLRs recorded under similar conditions in guinea pig, cat, and rat. Some qualitative similarities between gerbil and human MLRs are apparent. Results indicate that the MLR is a less sensitive measure of hearing threshold relative to the fast waves of the ABR at frequencies above 1 kHz. However, clearly defined MLRs are elicited with a wide range of stimulus frequencies. Because the surface recorded MLR reflects activation of central auditory pathways, including the cortex, it may provide an electrophysiological measure which can be utilized to study central components of normal and pathological auditory function.

Acoustic Stimulation↗

A human alphoid DNA clone from the EcoRI dimeric family: genomic and internal organization and chromosomal assignment.

We isolated an alpha satellite DNA clone (pC1.8), 17 kb long, which is composed exclusively of tandemly repeated 340-bp EcoRI fragments. Hybridization studies using 37 random EcoRI dimers subcloned from pC1.8 showed that they are heterogeneous. The sequence of 5 dimers, 3 of them adjacent, confirmed this observation and showed that the heterogeneity is more accentuated among the second monomers. The chromosomal assignment under high stringency conditions showed that this alphoid subset is located on chromosomes 1, 5, and 19. No conditions that eliminate the hybridization on any one of those chromosomes were found. This suggests that, in contrast to many other chromosome-specific alpha satellite subsets, the single chromosome subsets of this family are virtually indistinguishable by hybridization techniques.

Base Sequence↗

Saturation of human chromosome 3 with unique sequence hybridization probes.

We have generated chromosome 3-specific recombinant libraries in both lambda and cosmid cloning vectors starting with somatic cell hybrids (hamster/human) containing either an intact chromosome 3 or a chromosome 3 with an interstitial deletion removing 75% of long-arm sequences. The libraries contained between 2 X 10(5) and 5 X 10(6) independent recombinants. Approximately 2% of the recombinants in these libraries contain inserts of human DNA. These were identified by hybridizing the recombinants to radioactively labeled total human DNA. Over 2500 recombinants containing human DNA were isolated from these various libraries and DNA was prepared from each of them. This represents 80,000 kb of cloned chromosome 3 sequences. One-third of the DNAs were digested with EcoRI or HindIII, and fragments free of repetitive sequences were radioactively labeled using random hexanucleotide primers and tested as unique sequence hybridization probes. Over 6500 of the fragments were tested and of these 758 were unique sequence probes with minimal or no background hybridization. Their hybridization only to chromosome 3 was verified. These probes, which were derived from 452 independent recombinants, should provide an effective saturation of human chromosome 3.

Animals↗

Effect on liver cirrhosis and traffic accident mortality of changing the number and type of alcohol outlets in western Australia.

A longitudinal study with a 6-year before-period and a 9-year after-period was conducted to determine the effect of changing the number and type of alcohol outlets in Western Australia relative to a control State. During the 1974 to 1982 after-period Western Australia had a 16.0% increase in the hotel, tavern, and store rate in comparison to the control State, but a 17.4% decrease in the rate of licences for licensed clubs, restaurants, and all other licences. Consistent with previous correlational research, the above changes were associated with significant increases in Western Australia for male (+24.3%) and female (+29.3%) liver cirrhosis mortality, but a significant decrease in male driver and motorcyclist mortality (-22.1%). Attention is drawn to the value of longitudinal studies to examine both the negative and positive effects of changing the number and type of alcohol outlets.

Accidents, Traffic↗

Identification of two cosmids derived from within chromosomal band 3p21.1 that contain clusters of rare restriction sites and evolutionarily conserved sequences.

We have isolated large numbers of human recombinants from a cosmid library constructed from an interspecific (hamster/human) somatic cell hybrid whose only human component is an intact chromosome 3. Unique sequence probes were isolated from these recombinants and were used to localize them along the length of chromosome 3 by hybridization to a somatic cell hybrid deletion panel. We identified two cosmids, cA84 (D3S92) and cA199 (D3S93), derived from within chromosomal band 3p21.1. Both cosmids contained multiple rare restriction sites that were tightly clustered within the cosmids. We have therefore identified, in a region consistently deleted in a variety of lung cancers, two cosmids that may contain genes that are candidates for involvement in lung cancer.

Animals↗

Midline and temporal lobe MLRs in the guinea pig originate from different generator systems: a conceptual framework for new and existing data.

In the guinea pig and gerbil, individual components within the MLR time frame differ in optimal recording location. Specifically, MLR components obtained from the midline differ from those obtained over the temporal lobe. In the present paper midline and temporal lobe components were shown to differ not only in scalp topography but also in response to the following experimental manipulations: intracortical injection of neural inactivating agents (lidocaine and kainic acid), temporal lobe ablation, electrolytic lesions, systemic anesthesia, stimulation rate and course of development. Since midline and temporal lobe components respond differently to experimental manipulations, it can be concluded that the midline and temporal lobe responses are mediated by different generator sources. The particular orientation of the generators responsible for the MLR in the guinea pig and gerbil facilitates the identification of individual components. Results from simultaneous recordings of these components during experimental manipulations support the hypothesis of multiple MLR generators in laboratory animals and provide insight into the generators and developmental aspects of the MLR in humans.

Acoustic Stimulation↗

Effect on traffic accidents of introducing Sunday alcohol sales in Brisbane, Australia.

Following introduction of Sunday alcohol sale sessions in Brisbane, there were significant increases in the number of Sunday casualty and reported property damage accidents. The increases still applied during a second 3-year after period. By contrast, none of the various control comparisons gave significant results in the same direction. It was concluded that the study had documented the ongoing adverse effect on traffic accidents of introducing Sunday sessions in Brisbane.

Accidents, Traffic↗

Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel.

A series of human chromosome 3-specific DNA fragments isolated and characterized from a lamda phage genomic library were regionally localized on human chromosome 3. This was accomplished using filter hybridization blot analysis of a human chromosome 3 hybrid cell deletion mapping panel. Twenty-three new anonymous DNA fragments were assigned to one of four physical regions of chromosome 3. Seventeen DNA fragments were mapped to the long arm of chromosome 3, including one DNA fragment that demonstrated a restriction fragment length polymorphism (RFLP). Five DNA fragments were assigned to 3p14.2----pter, including one highly polymorphic fragment sublocalized at 3p25----pter by in situ hybridization. This DNA fragment is the second reported distal 3p polymorphic probe. One DNA fragment was localized to 3p14----p14.2. In addition, three fragments previously assigned to chromosome 3 were confirmed. Polymorphic DNA probes DNF15S2 (formerly D1S1) and D3S2 were mapped to 3p14.2----pter. The previous 3p25 in situ localization of the c-raf-1 oncogene was supported by deletion panel mapping. The physical localization of these twenty-three new DNA fragments has more than doubled the number of cloned DNA fragments assigned to chromosome 3. These and future regional assignments of DNA fragment probes will facilitate construction of both a physical and genetic linkage map of chromosome 3. They may also be useful in characterizing the chromosomal and molecular aberrations involved in small-cell lung cancer (SCLC), renal cell carcinoma, other malignancies, and the 3p14.2 common fragile site.

Bacteriophage lambda↗

Overabundance of rare-cutting restriction endonuclease sites in the human genome.

A human chromosome 3-specific cosmid library was constructed from a somatic cell hybrid containing human chromosome 3 as its only human component. This library was screened to identify 230 human recombinants which contained an average insert size of 37 kilobases. DNA prepared from 54 of these cosmids, representing 2000 kilobases of human DNA, was then tested for restriction endonuclease sites for EcoRI, HindIII, KpnI, XhoI, and DraI, as well as those of the rare-cutting restriction endonucleases NotI, SfiI, NruI, MluI, SacII, and BssHII. Sites for the latter enzymes were much more abundant than would be expected from theoretical calculations, reflecting non-random clustering of these sites. This has important implications for the use of these enzymes in the construction of physical maps of chromosomes. Some individual cosmids contained large numbers of rare sites, offering an alternative means of physically mapping chromosomes based upon identifying clusters of rare restriction sites. These clusters appear to be spaced an average of 1000 kb apart.

Animals↗

Subtotal premaxillectomy; a salvage procedure in selected cases of bilateral cleft lip and palate.

Subtotal premaxillectomy with preservation of the posterior plate of the premaxilla and the premaxillary-vomerine suture line was carried out in six selected cases of severe bilateral cleft lip and palate between the ages of four and eight years. The long term results are shown and it is concluded that although the procedure does not seem to affect mid-facial growth adversely, it should be reserved for very selective cases and only as a last resort.

Child↗

High-pass filter settings affect the detectability of MLRs in humans.

Auditory middle latency responses (MLRs) have been recorded in 217 patients ranging in age from 6 days to 20 years. The probability of obtaining MLR components Na and Pa was higher with a high-pass filter setting of 15 Hz, 12 dB/octave as compared to 3 Hz, 6 dB/octave. This effect was found at all ages tested. Age-related latency effects were apparent with 3 Hz but not 15 Hz filtering.

Adolescent↗

Postnatal development of the auditory brainstem response (ABR) in the unanesthetized gerbil.

The auditory brainstem response (ABR) was used to study the development of 8th nerve and auditory brainstem function in 71 unanesthetized gerbils. Initial replicable responses were observed on day 14. Six vertex-positive waves and a slow negative response (SNR) were obtained in response to a 100 dB HL (re adult threshold) click stimulus on day 20. A general pattern of development characterized by decreasing threshold and wave latencies and increasing amplitudes was found. Latency changes occurred in two stages; rapid decreases in the third postnatal week, followed by a period of gradual decline toward adult latencies during the fourth and fifth weeks. Greater changes in absolute latency were observed for later waves. Development of adult-like thresholds and resistance of response detectability (presence or absence) to increasing stimulus rates occurred prior to or simultaneous with maturation of wave latencies. Increases in amplitude with age continued to adulthood for waves IV and SNR, while other waves declined in amplitude after day 20. The maturation of the ABR overlapped with the emergence and development of the auditory middle latency response (MLR). Waves B (adult latency 16 ms) and C (adult latency 25 ms) were discernable at approximately the same age that a replicable ABR was first obtained, and wave A (adult latency 14 ms) shortly thereafter. The general pattern of decreasing ABR wave thresholds and latencies with age seen in the gerbil is similar to that found in other mammals, including humans. However, the development of mature response characteristics appeared to proceed at a somewhat independent rate among the different ABR and MLR waves. The emergence of the MLR before several ABR waves suggests that development of auditory function in the gerbil may not follow a strictly sequential pattern.

Age Factors↗

Development of the middle latency response in an animal model and its relation to the human response.

Although the clinical use of the middle latency response (MLR) in adults is fairly straightforward, its use is complicated by maturational changes that continue throughout the first decade of life. In order to telescope the time period of this long developmental course, we have approached the study of MLR maturation using the gerbil as an animal model. The course of MLR obtained over the temporal lobe development was characterized in the Mongolian gerbil ranging in age from 10 days to 3 months of life. The adult gerbil MLR consists of two positive peaks (A and C) at 11 and 25 ms, respectively, and a negative component (B) at 16 ms. These components emerge in a systematic fashion as a function of age. The present work supports a strong age effect of increased MLR detectability in the gerbil, similar to findings reported for humans. Wave A was infrequently detected in young animals, but when present, it occurred at adult latencies. The latency of waves B and C decreased systematically with age. The amplitude of all components increased with age, similar to findings in humans. The fact that adult-like thresholds were obtained shortly after birth indicates that when present, MLRs may be a good index of hearing threshold. Effects of stimulating across a wide range of intensities were described. The gerbil model appears appropriate for the study of development of the central auditory system function.

Age Factors↗